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Gao L, Zhang Y, Hu Z, Chen S, Wang Q, Zeng Y, Yin H, Zhao J, Zhan Y, Gao C, Xin Y, Chen B, van der Veen S, Zhao M, Fang D, Lu Q. Microbiota-Derived Inosine Suppresses Systemic Autoimmunity via Restriction of B Cell Differentiation and Migration. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2409837. [PMID: 40289872 PMCID: PMC12120789 DOI: 10.1002/advs.202409837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Revised: 02/27/2025] [Indexed: 04/30/2025]
Abstract
The role of gut microbiota dysbiosis in systemic lupus erythematosus (SLE) pathogenesis remains elusive. Here, it is shown that fecal microbiota transplantation (FMT) from healthy mice to lupus mice ameliorates lupus-like symptoms. Microbiota reconstitution effectively reduces systemic class switch recombination (CSR) and elevates immunoglobulin heavy chain (IGH) naïve isotype. Microbiota profiling reveals an enrichment of Lactobacillus johnsonii post-FMT, with a significant correlation to purine metabolites. Importantly, the L. johnsonii-derived inosine, an intermediate metabolite in purine metabolism, effectively alleviates lupus pathogenesis in mice. Inosine inhibits B cell differentiation and reduces renal B cell infiltration to protect mice from lupus. At the molecular level, inosine reprograms B cells through the extracellular signal-regulated kinase (ERK)-hypoxia-inducible factor-1alpha (HIF-1α) signaling pathway. Therefore, this study highlights the discovery of a novel microbial metabolite modulating autoimmunity and suggests its potential for innovative microbiome-based therapeutic approaches.
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Affiliation(s)
- Lingyu Gao
- Hospital for Skin DiseasesInstitute of DermatologyChinese Academy of Medical Sciences and Peking Union Medical CollegeNanjing210042China
- Key Laboratory of Basic and Translational Research on Immune‐Mediated Skin DiseasesChinese Academy of Medical SciencesNanjing210042China
- Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIsNanjing210042China
| | - Yuhan Zhang
- Hospital for Skin DiseasesInstitute of DermatologyChinese Academy of Medical Sciences and Peking Union Medical CollegeNanjing210042China
- Key Laboratory of Basic and Translational Research on Immune‐Mediated Skin DiseasesChinese Academy of Medical SciencesNanjing210042China
- Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIsNanjing210042China
| | - Zhi Hu
- Hospital for Skin DiseasesInstitute of DermatologyChinese Academy of Medical Sciences and Peking Union Medical CollegeNanjing210042China
- Key Laboratory of Basic and Translational Research on Immune‐Mediated Skin DiseasesChinese Academy of Medical SciencesNanjing210042China
- Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIsNanjing210042China
| | - Shengwen Chen
- Hospital for Skin DiseasesInstitute of DermatologyChinese Academy of Medical Sciences and Peking Union Medical CollegeNanjing210042China
- Key Laboratory of Basic and Translational Research on Immune‐Mediated Skin DiseasesChinese Academy of Medical SciencesNanjing210042China
- Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIsNanjing210042China
| | - Qiaolin Wang
- Hospital for Skin DiseasesInstitute of DermatologyChinese Academy of Medical Sciences and Peking Union Medical CollegeNanjing210042China
- Key Laboratory of Basic and Translational Research on Immune‐Mediated Skin DiseasesChinese Academy of Medical SciencesNanjing210042China
- Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIsNanjing210042China
| | - Yong Zeng
- Hunan Key Laboratory of Medical EpigenomicsThe Second Xiangya HospitalCentral South UniversityChangsha410013China
| | - Huiqi Yin
- Hospital for Skin DiseasesInstitute of DermatologyChinese Academy of Medical Sciences and Peking Union Medical CollegeNanjing210042China
- Key Laboratory of Basic and Translational Research on Immune‐Mediated Skin DiseasesChinese Academy of Medical SciencesNanjing210042China
- Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIsNanjing210042China
| | - Junpeng Zhao
- Hospital for Skin DiseasesInstitute of DermatologyChinese Academy of Medical Sciences and Peking Union Medical CollegeNanjing210042China
- Key Laboratory of Basic and Translational Research on Immune‐Mediated Skin DiseasesChinese Academy of Medical SciencesNanjing210042China
- Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIsNanjing210042China
| | - Yijing Zhan
- Hospital for Skin DiseasesInstitute of DermatologyChinese Academy of Medical Sciences and Peking Union Medical CollegeNanjing210042China
- Key Laboratory of Basic and Translational Research on Immune‐Mediated Skin DiseasesChinese Academy of Medical SciencesNanjing210042China
- Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIsNanjing210042China
| | - Changxing Gao
- Hospital for Skin DiseasesInstitute of DermatologyChinese Academy of Medical Sciences and Peking Union Medical CollegeNanjing210042China
- Key Laboratory of Basic and Translational Research on Immune‐Mediated Skin DiseasesChinese Academy of Medical SciencesNanjing210042China
- Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIsNanjing210042China
| | - Yue Xin
- Hospital for Skin DiseasesInstitute of DermatologyChinese Academy of Medical Sciences and Peking Union Medical CollegeNanjing210042China
- Key Laboratory of Basic and Translational Research on Immune‐Mediated Skin DiseasesChinese Academy of Medical SciencesNanjing210042China
- Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIsNanjing210042China
| | - Bing Chen
- Clinical LaboratoryThe Second Hospital of Anhui Medical UniversityHefei230601China
| | - Stijn van der Veen
- Department of Microbiologyand Department of DermatologySir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhou310058China
| | - Ming Zhao
- Hospital for Skin DiseasesInstitute of DermatologyChinese Academy of Medical Sciences and Peking Union Medical CollegeNanjing210042China
- Key Laboratory of Basic and Translational Research on Immune‐Mediated Skin DiseasesChinese Academy of Medical SciencesNanjing210042China
- Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIsNanjing210042China
- Hunan Key Laboratory of Medical EpigenomicsThe Second Xiangya HospitalCentral South UniversityChangsha410013China
| | - Deyu Fang
- Department of PathologyNorthwestern University Feinberg School of MedicineChicagoIL60611USA
| | - Qianjin Lu
- Hospital for Skin DiseasesInstitute of DermatologyChinese Academy of Medical Sciences and Peking Union Medical CollegeNanjing210042China
- Key Laboratory of Basic and Translational Research on Immune‐Mediated Skin DiseasesChinese Academy of Medical SciencesNanjing210042China
- Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIsNanjing210042China
- Hunan Key Laboratory of Medical EpigenomicsThe Second Xiangya HospitalCentral South UniversityChangsha410013China
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Zhang J, Yang Z, Liu X, Yang X, Li Y, Jin X, Duan H, Chen H, Zhao W, Wang Q, Liu Y. New Insights into the Pathogenesis of Alcoholic Liver Disease Based on Global Research. Dig Dis Sci 2025; 70:903-918. [PMID: 39806089 DOI: 10.1007/s10620-024-08778-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 11/24/2024] [Indexed: 01/16/2025]
Abstract
BACKGROUND AND AIMS Alcoholic liver disease (ALD) is the leading cause of death among alcohol-related diseases, yet its pathogenesis remains incompletely understood. This article employs data mining methods to conduct an indepth study of articles on ALD published in the past three decades, aiming to elucidate the pathogenesis of ALD. METHODS Firstly, articles related to the pathogenesis of ALD were retrieved from the Web of Science (WOS) database. CiteSpace 6.1.R2 and VOSviewer 1.6.18 were used to visually analyze the authors, institutions, journals, and keywords of the published articles. Secondly, by thoroughly reading the top 100 most cited articles and focusing on research hotspots such as cytochrome P450 2E1 (CYP2E1), gut microbiota, acetaldehyde dehydrogenase (ALDH), and alcohol dehydrogenase (ADH), the pathogenesis of ALD was preliminarily explored. Finally, the pathogenesis of ALD was further analyzed based on disease databases. RESULTS A total of 1521 articles were retrieved from the WOS database, and 384 of these were selected for in-depth reading. From GeneCards, 9084 genes related to ALD were identified. KEGG enrichment analysis was performed using DAVID, and the hsa04936: Alcoholic liver disease pathway was selected for visualization. CONCLUSIONS This study preliminarily elucidates the pathogenesis of ALD, which may be associated with the release of acetaldehyde, reactive oxygen species (ROS), and various pro-inflammatory factors during alcohol metabolism. It is also closely related to gut microbiota dysbiosis and increased intestinal permeability induced by multiple factors.
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Affiliation(s)
- Jinbao Zhang
- College of Pharmacy, Gansu University of Chinese Medicine, No.35 Dingxi East Road, Chengguan District, Lanzhou, China.
- Northwest Collaborative Innovation Center for Traditional Chinese Medicine Co-constructed by Gansu Province & MOE of PRC, Lanzhou, China.
- Key Laboratory of Pharmacology and Toxicology of TCM in Gansu Province, Lanzhou, China.
- Engineering Research Center for Evaluation, Protection and Utilization of Rare Traditional Chinese Medicine Resources, Lanzhou, Gansu, China.
| | - Zonghui Yang
- College of Pharmacy, Gansu University of Chinese Medicine, No.35 Dingxi East Road, Chengguan District, Lanzhou, China
| | - Xiaona Liu
- College of Pharmacy, Gansu University of Chinese Medicine, No.35 Dingxi East Road, Chengguan District, Lanzhou, China
| | - Xiujuan Yang
- College of Pharmacy, Gansu University of Chinese Medicine, No.35 Dingxi East Road, Chengguan District, Lanzhou, China
- Northwest Collaborative Innovation Center for Traditional Chinese Medicine Co-constructed by Gansu Province & MOE of PRC, Lanzhou, China
- Key Laboratory of Pharmacology and Toxicology of TCM in Gansu Province, Lanzhou, China
| | - Yaling Li
- Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and The Prevention and Treatment With Traditional Chinese Medicine Research in Gansu Colleges and University, Gansu University of Chinese Medicine, Lanzhou, China
| | - Xiaojie Jin
- College of Pharmacy, Gansu University of Chinese Medicine, No.35 Dingxi East Road, Chengguan District, Lanzhou, China
- Northwest Collaborative Innovation Center for Traditional Chinese Medicine Co-constructed by Gansu Province & MOE of PRC, Lanzhou, China
- Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and The Prevention and Treatment With Traditional Chinese Medicine Research in Gansu Colleges and University, Gansu University of Chinese Medicine, Lanzhou, China
| | - Haijing Duan
- College of Pharmacy, Gansu University of Chinese Medicine, No.35 Dingxi East Road, Chengguan District, Lanzhou, China
- Northwest Collaborative Innovation Center for Traditional Chinese Medicine Co-constructed by Gansu Province & MOE of PRC, Lanzhou, China
- Key Laboratory of Pharmacology and Toxicology of TCM in Gansu Province, Lanzhou, China
| | - Honggang Chen
- College of Pharmacy, Gansu University of Chinese Medicine, No.35 Dingxi East Road, Chengguan District, Lanzhou, China
- Northwest Collaborative Innovation Center for Traditional Chinese Medicine Co-constructed by Gansu Province & MOE of PRC, Lanzhou, China
- Engineering Research Center for Evaluation, Protection and Utilization of Rare Traditional Chinese Medicine Resources, Lanzhou, Gansu, China
| | - Wenlong Zhao
- College of Pharmacy, Gansu University of Chinese Medicine, No.35 Dingxi East Road, Chengguan District, Lanzhou, China
- Northwest Collaborative Innovation Center for Traditional Chinese Medicine Co-constructed by Gansu Province & MOE of PRC, Lanzhou, China
- Engineering Research Center for Evaluation, Protection and Utilization of Rare Traditional Chinese Medicine Resources, Lanzhou, Gansu, China
| | - Qian Wang
- Clinical College of Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, China
| | - Yongqi Liu
- Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and The Prevention and Treatment With Traditional Chinese Medicine Research in Gansu Colleges and University, Gansu University of Chinese Medicine, Lanzhou, China
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Xu J, Chen N, Li Z, Liu Y. Gut microbiome and liver diseases. FUNDAMENTAL RESEARCH 2025; 5:890-901. [PMID: 40242515 PMCID: PMC11997574 DOI: 10.1016/j.fmre.2024.09.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 09/18/2024] [Accepted: 09/20/2024] [Indexed: 04/18/2025] Open
Abstract
Symbiotic microbiota plays a crucial role in the education, development, and maintenance of the host immune system, significantly contributing to overall health. Through the gut-liver axis, the gut microbiota and liver have a bidirectional relationship that is becoming increasingly evident as more research highlights the translocation of the gut microbiota and its metabolites. The focus of this narrative review is to examine and discuss the importance of the gut-liver axis and the enterohepatic barrier in maintaining overall health. Additionally, we emphasize the crucial role of the gut microbiome in liver diseases and explore potential therapeutic strategies for liver diseases by manipulating the microbiota.
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Affiliation(s)
- Jun Xu
- Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, China
- Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing 100044, China
| | - Ning Chen
- Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, China
- Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing 100044, China
| | - Zhou Li
- Beijing Key Laboratory of Micro-nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems Chinese Academy of Sciences, Beijing 101400, China
- School of Nanoscience and Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yulan Liu
- Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, China
- Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing 100044, China
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Yang F, Li X, Sun J, Pang X, Sun Q, Lu Y. Regulatory mechanisms of the probiotic-targeted gut-liver axis for the alleviation of alcohol-related liver disease: a review. Crit Rev Food Sci Nutr 2025:1-22. [PMID: 39905925 DOI: 10.1080/10408398.2025.2455954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2025]
Abstract
Alcohol abuse-triggered alcohol-related liver disease (ALD) has become as a global public health concern that substantially affects the well-being and clinical status of patients. Although modern medicine provides various treatments for ALD, their effectiveness is limited and can lead to adverse side effects. Probiotics have been employed to prevent, alleviate, and even treat ALD, with promising results. However, few comprehensive reviews are available on how they mitigate ALD by targeting the gut-liver axis. This review systematically clarifies the specific mediators of the gut-liver axis in healthy states. It also describes the alterations observed in ALD. Furthermore, this review thoroughly summarizes the underlying mechanisms through which probiotics act on the gut-liver axis to relieve ALD. It also discusses the current status and challenges faced in clinical research applications. Finally, we discuss the challenges and future prospects of using probiotics to treat ALD. This review improves our understanding of ALD and supports the development and application of probiotics that target the gut-liver axis for therapeutic use.
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Affiliation(s)
- Feiyu Yang
- College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing, China
- College of Food Science and Technology, Nanjing Agricultural University, Nanjing, China
| | - Xiangfei Li
- College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing, China
| | - Jing Sun
- College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing, China
| | - Xinyi Pang
- College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing, China
| | - Quancai Sun
- Department of Health, Nutrition, and Food Sciences, Florida State University, Tallahassee, FL, USA
| | - Yingjian Lu
- College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing, China
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Tang S, Wu S, Zhang W, Ma L, Zuo L, Wang H. Immunology and treatments of fatty liver disease. Arch Toxicol 2025; 99:127-152. [PMID: 39692857 DOI: 10.1007/s00204-024-03920-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 11/26/2024] [Indexed: 12/19/2024]
Abstract
Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are two major chronic liver diseases worldwide. The triggers for fatty liver can be derived from external sources such as adipose tissue, the gut, personal diet, and genetics, or internal sources, including immune cell responses, lipotoxicity, hepatocyte death, mitochondrial dysfunction, and extracellular vesicles. However, their pathogenesis varies to some extent. This review summarizes various immune mechanisms and therapeutic targets associated with these two types of fatty liver disease. It describes the gut-liver axis and adipose tissue-liver crosstalk, as well as the roles of different immune cells (both innate and adaptive immune cells) in fatty liver disease. Additionally, mitochondrial dysfunction, extracellular vesicles, microRNAs (miRNAs), and gastrointestinal hormones are also related to the pathogenesis of fatty liver. Understanding the pathogenesis of fatty liver and corresponding therapeutic strategies provides a new perspective for developing novel treatments for fatty liver disease.
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Affiliation(s)
- Sainan Tang
- Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, Anhui, China
- Laboratory of Molecular Biology, Department of Biochemistry, School of Basic Medical Science, Anhui Medical University, Hefei, 230022, Anhui, China
| | - Shanshan Wu
- Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, Anhui, China
- Department of Gastroenterology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
- Inflammation and Immune-Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, Anhui, China
| | - Wenzhe Zhang
- Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, Anhui, China
- The First College of Clinical Medicine, Anhui Medical University, Hefei, Anhui, China
| | - Lili Ma
- Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, Anhui, China
- The First College of Clinical Medicine, Anhui Medical University, Hefei, Anhui, China
| | - Li Zuo
- Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, Anhui, China.
- Laboratory of Molecular Biology, Department of Biochemistry, School of Basic Medical Science, Anhui Medical University, Hefei, 230022, Anhui, China.
| | - Hua Wang
- Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China.
- Inflammation and Immune-Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, Anhui, China.
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Li W, Gao W, Yan S, Yang L, Zhu Q, Chu H. Gut Microbiota as Emerging Players in the Development of Alcohol-Related Liver Disease. Biomedicines 2024; 13:74. [PMID: 39857657 PMCID: PMC11761646 DOI: 10.3390/biomedicines13010074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2024] [Revised: 12/23/2024] [Accepted: 12/29/2024] [Indexed: 01/27/2025] Open
Abstract
The global incidence and mortality rates of alcohol-related liver disease are on the rise, reflecting a growing health concern worldwide. Alcohol-related liver disease develops due to a complex interplay of multiple reasons, including oxidative stress generated during the metabolism of ethanol, immune response activated by immunogenic substances, and subsequent inflammatory processes. Recent research highlights the gut microbiota's significant role in the progression of alcohol-related liver disease. In patients with alcohol-related liver disease, the relative abundance of pathogenic bacteria, including Enterococcus faecalis, increases and is positively correlated with the level of severity exhibited by alcohol-related liver disease. Supplement probiotics like Lactobacillus, as well as Bifidobacterium, have been found to alleviate alcohol-related liver disease. The gut microbiota is speculated to trigger specific signaling pathways, influence metabolite profiles, and modulate immune responses in the gut and liver. This research aimed to investigate the role of gut microorganisms in the onset and advancement of alcohol-related liver disease, as well as to uncover the underlying mechanisms by which the gut microbiota may contribute to its development. This review outlines current treatments for reversing gut dysbiosis, including probiotics, fecal microbiota transplantation, and targeted phage therapy. Particularly, targeted therapy will be a vital aspect of future alcohol-related liver disease treatment. It is to be hoped that this article will prove beneficial for the treatment of alcohol-related liver disease.
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Affiliation(s)
- Wei Li
- Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Hubei Clinical Research Center for Infectious Diseases, Wuhan Research Center for Communicable Disease Diagnosis and Treatment, Chinese Academy of Medical Sciences, Joint Laboratory of Infectious Diseases and Health, Wuhan Institute of Virology and Wuhan Jinyintan Hospital, Chinese Academy of Sciences, Wuhan 430023, China;
| | - Wenkang Gao
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (W.G.); (S.Y.); (L.Y.)
| | - Shengqi Yan
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (W.G.); (S.Y.); (L.Y.)
| | - Ling Yang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (W.G.); (S.Y.); (L.Y.)
| | - Qingjing Zhu
- Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Hubei Clinical Research Center for Infectious Diseases, Wuhan Research Center for Communicable Disease Diagnosis and Treatment, Chinese Academy of Medical Sciences, Joint Laboratory of Infectious Diseases and Health, Wuhan Institute of Virology and Wuhan Jinyintan Hospital, Chinese Academy of Sciences, Wuhan 430023, China;
| | - Huikuan Chu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (W.G.); (S.Y.); (L.Y.)
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Wu J, Lyu S, Guo D, Yang N, Liu Y. Protective effects of YCHD on the autoimmune hepatitis mice model induced by Ad-CYP2D6 through modulating the Th1/Treg ratio and intestinal flora. Front Immunol 2024; 15:1488125. [PMID: 39606230 PMCID: PMC11600021 DOI: 10.3389/fimmu.2024.1488125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 09/30/2024] [Indexed: 11/29/2024] Open
Abstract
Background Autoimmune hepatitis (AIH) is a chronic liver inflammatory disease mediated by autoimmune reactions, the pathogenesis of AIH is probably related to the imbalance of intestinal flora. Yinchenhao decoction (YCHD) has been used to relieve AIH. However, the mechanisms underpinning YCHD's hepatoprotective effects with the gut microbito have not been fully revealed. Objective To explore the potential mechanism of YCHD in treating AIH based on changes in the intestinal flora and Th1/Treg ratio in the spleen and hepatic hilar lymph nodes. Methods The AIH mice model induced by the adenovirus vectors that overexpress human cytochrome P450 family 2 subfamily D member 6 (Ad-CYP2D6) was established (untreated group). One week after the Ad-CYP2D6 injection, the AIH model mice were treated by administering YCHD by gavage for 14 days (YCHD-treated group). The therapeutic efficacy of YCHD on AIH was evaluated by detecting the histopathological changes of the liver, serum transaminases (ALT and AST), inflammatory factors (TNF-α,IL-17 and IFN-γ), and autoantibodies (including LKM-1 and LC-1). The ratio of Th1 to Treg within the spleen and hepatic hilar lymph nodes of the mice was detected by flow cytometry. The changes in the species and abundance of intestinal flora and intestinal flora metabolites were analyzed via 16S rRNA gene sequencing and gas chromatography-mass spectrometry (GC/MS) to reveal the protective mechanism of YCHD on liver injury. Result YCHD decreased the transaminase activity (AST and ALT), the content of autoantibodies (LC-1 and LKM-1), and the serum TNF-α, IL-12, and IL-17 levels in AIH mice. The degree of inflammatory infiltration in the YCHD-treated group was significantly less than that in the untreated group. YCHD can effectively reverse the abundance and diversity of intestinal flora in AIH mice and affect the release of short-chain fatty acids (SCFAs), especially butyric acid. Moreover, the flow cytometry results showed that YCHD could also decline the ratio of Th1/Treg, which probably be induced by SCFAs via the G protein-coupled receptor (GPR). Conclusion YCHD may affect the release of SCFAs by regulating the intestinal microbiota, thereby affecting the differentiation of Th1 and Treg, and achieving the effect of alleviating liver damage.
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Affiliation(s)
- Jiawen Wu
- College of Basic Medical Sciences, Shanxi University of Chinese Medicine, Jinzhong, China
- Basic Laboratory of Integrated Traditional Chinese and Western Medicine, Shanxi University of Chinese Medicine, Jinzhong, China
- Engineering Research Center of Cross Innovation for Chinese Traditional Medicine of Shanxi Province, Jinzhong, China
| | - Sixue Lyu
- College of Basic Medical Sciences, Shanxi University of Chinese Medicine, Jinzhong, China
- Basic Laboratory of Integrated Traditional Chinese and Western Medicine, Shanxi University of Chinese Medicine, Jinzhong, China
- Engineering Research Center of Cross Innovation for Chinese Traditional Medicine of Shanxi Province, Jinzhong, China
| | - Di Guo
- College of Basic Medical Sciences, Shanxi University of Chinese Medicine, Jinzhong, China
- Basic Laboratory of Integrated Traditional Chinese and Western Medicine, Shanxi University of Chinese Medicine, Jinzhong, China
- Engineering Research Center of Cross Innovation for Chinese Traditional Medicine of Shanxi Province, Jinzhong, China
| | - Na Yang
- College of Basic Medical Sciences, Shanxi University of Chinese Medicine, Jinzhong, China
- Basic Laboratory of Integrated Traditional Chinese and Western Medicine, Shanxi University of Chinese Medicine, Jinzhong, China
- Engineering Research Center of Cross Innovation for Chinese Traditional Medicine of Shanxi Province, Jinzhong, China
| | - Yang Liu
- College of Basic Medical Sciences, Shanxi University of Chinese Medicine, Jinzhong, China
- Basic Laboratory of Integrated Traditional Chinese and Western Medicine, Shanxi University of Chinese Medicine, Jinzhong, China
- Engineering Research Center of Cross Innovation for Chinese Traditional Medicine of Shanxi Province, Jinzhong, China
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Wang XY, Meng FH, Zhang MY, Li FX, Lei YX, Ma ZG, Li JQ, Lou YN, Chu YF, Ma K, Yu SX. Gut Lactococcus garvieae promotes protective immunity to foodborne Clostridium perfringens infection. Microbiol Spectr 2024; 12:e0402523. [PMID: 39190634 PMCID: PMC11448249 DOI: 10.1128/spectrum.04025-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Accepted: 07/19/2024] [Indexed: 08/29/2024] Open
Abstract
The gut microbiota, a pivotal component of the intestinal mucosal barrier, is critical for host resistance to enteric pathogen infection. Here, we report a novel function of the potentially probiotic Lactococcus garvieae strain LG1 (L. garvieae strain LG1) in maintaining intestinal mucosal barrier integrity and protecting against foodborne Clostridium perfringens (C. perfringens) infection. L. garvieae was isolated from the intestinal contents of Chinese Mongolian sheep (MS) and exhibited potential probiotic properties. In a C. perfringens enterocolitis model, L. garvieae-pretreated mice were less susceptible to C. perfringens infection compared with Phosphate buffered solution (PBS)-pretreated mice, which manifested as higher survival rates, lower pathogen loads, less weight loss, mild clinical symptoms and intestinal damage, and minor inflammation. Further mechanistic analysis showed that L. garvieae could ameliorate the disruption of intestinal permeability and maintain the integrity of the intestinal mucosal barrier by promoting the expression of tight junction proteins and mucoproteins. Moreover, L. garvieae was also able to facilitate antimicrobial peptide expression and ameliorate dysbiosis of the gut microbiota caused by C. perfringens. Together, these findings highlight the prospect of immunomodulatory potentially probiotic L. garvieae and might offer valuable strategies for prophylaxis and/or treatment of pathogenic C. perfringens mucosal infection. IMPORTANCE C. perfringens necrotic enteritis leads to losses of about US $2 billion to the poultry industry worldwide every year. Worse, US Centers for Disease Control and Prevention (CDC) has estimated that C. perfringens causes nearly 1 million foodborne illnesses in the United States annually. Nowadays, the treatment recommendation is a combination of a broad-spectrum synergistic penicillin with clindamycin or a carbapenem, despite growing scientific concern over antibiotic resistance. The global understanding of the gut microbiome for C. perfringens infection may provide important insights into the intervention. L. garvieae originated from Mongolian sheep intestine, exhibited potentially probiotic properties, and was able to limit C. perfringens enterocolitis and pathogenic colonization. Importantly, we found that L. garvieae limits C. perfringens invasion via improving intestinal mucosal barrier function. Also, L. garvieae alleviates C. perfringens-induced gut microbiota dysbiosis. It allowed us to convince that utilization of probiotics to promote protective immunity against pathogens infection is of pivotal importance.
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Affiliation(s)
- Xue-Yin Wang
- State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, China
| | - Fan-Hua Meng
- State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, China
| | - Ming-Yue Zhang
- State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, China
| | - Fen-Xin Li
- State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, China
| | - Yu-Xin Lei
- State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, China
| | - Zhao-Guo Ma
- State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, China
| | - Jia-Qi Li
- State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, China
| | - Ya-Nan Lou
- State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, China
| | - Yue-Feng Chu
- State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy agricultural Sciences, Lanzhou, China
| | - Ke Ma
- State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy agricultural Sciences, Lanzhou, China
| | - Shui-Xing Yu
- State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, China
- Inner Mongolia Engineering Technology Research Center of Germplasm Resources Conservation and Utilization, College of Life Sciences, Inner Mongolia University, Hohhot, China
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9
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Lv J, Lang G, Wang Q, Zhao W, Shi D, Zhou Z, Shen Y, Xia H, Han S, Li L. Lactobacillus helveticus attenuates alcoholic liver injury via regulation of gut microecology in mice. Microb Biotechnol 2024; 17:e70016. [PMID: 39431804 PMCID: PMC11492535 DOI: 10.1111/1751-7915.70016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2023] [Accepted: 09/04/2024] [Indexed: 10/22/2024] Open
Abstract
Previous reports have demonstrated that alcohol consumption significantly reduces the abundance of Lactobacillus in the gut. In this study, we selected five species of the genus Lactobacillus, commonly found in fermented foods, and acknowledged them as safe, edible, and effective in preventing or treating certain diseases, to evaluate their effects on alcoholic liver disease (ALD). By comparing the liver damage indices in each group, we found that the type strain of Lactobacillus helveticus (LH, ATCC 15009) had the most marked alleviating effect on ALD-induced liver injury. Furthermore, experiments combining microbiomics and metabolomics were conducted to explore the mechanisms underlying the hepatoprotective effects of LH. Finally, we discovered that LH mitigated ethanol-induced liver steatosis and inflammation in ALD mice by altering the structure and function of the gut microbiome, increasing intestinal levels of short-chain fatty acids (SCFAs), and enhancing gut barrier integrity. These findings suggest a potential strategy for the clinical management of patients with ALD.
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Affiliation(s)
- Jiawen Lv
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
- College of MedicineZhejiang UniversityHangzhouChina
| | - Guanjing Lang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Qiangqiang Wang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Wenlong Zhao
- Beijing Tsinghua Changgung Hospital, School of Clinical MedicineTsinghua UniversityBeijingChina
| | - Ding Shi
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Ziyuan Zhou
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
- College of MedicineZhejiang UniversityHangzhouChina
| | - Yangfan Shen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
- College of MedicineZhejiang UniversityHangzhouChina
| | - He Xia
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
- College of MedicineZhejiang UniversityHangzhouChina
| | - Shengyi Han
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
- College of MedicineZhejiang UniversityHangzhouChina
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
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10
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Zhang LL, Xu JY, Xing Y, Wu P, Jin YW, Wei W, Zhao L, Yang J, Chen GC, Qin LQ. Lactobacillus rhamnosus GG alleviates radiation-induced intestinal injury by modulating intestinal immunity and remodeling gut microbiota. Microbiol Res 2024; 286:127821. [PMID: 38941923 DOI: 10.1016/j.micres.2024.127821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 06/23/2024] [Accepted: 06/24/2024] [Indexed: 06/30/2024]
Abstract
Radiation injury to the intestine is one of the most common complications in patients undergoing abdominal or pelvic cavity radiotherapy. In this study, we investigated the potential protective effect of Lactobacillus rhamnosus GG (LGG) on radiation-induced intestinal injury and its underlying mechanisms. Mice were assigned to a control group, a 10 Gy total abdominal irradiation (TAI) group, or a group pretreated with 108 CFU LGG for three days before TAI. Small intestine and gut microbiota were analyzed 3.5 days post-exposure. LGG intervention improved intestinal structure, reduced jejunal DNA damage, and inhibited the inflammatory cGAS/STING pathway. Furthermore, LGG reduced M1 proinflammatory macrophage and CD8+ T cell infiltration, restoring the balance between Th17 and Treg cells in the inflamed jejunum. LGG also partially restored the gut microbiota. These findings suggest the possible therapeutic radioprotective effect of probiotics LGG in alleviating radiation-induced intestinal injury by maintaining immune homeostasis and reshaping gut microbiota.
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Affiliation(s)
- Li-Li Zhang
- Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Ren'ai Road, Suzhou 215123, China
| | - Jia-Ying Xu
- State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, 199 Ren'ai Road, Suzhou 215123, China
| | - Yifei Xing
- Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Ren'ai Road, Suzhou 215123, China
| | - Pengcheng Wu
- Zhangjiagang Center for Disease Control and Prevention, 18 Zhizhong Road, Zhangjiagang 215600, China
| | - Yi-Wen Jin
- Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Ren'ai Road, Suzhou 215123, China
| | - Wei Wei
- State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, 199 Ren'ai Road, Suzhou 215123, China
| | - Lin Zhao
- State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, 199 Ren'ai Road, Suzhou 215123, China
| | - Jing Yang
- Department of Clinical Nutrition, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, China
| | - Guo-Chong Chen
- Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Ren'ai Road, Suzhou 215123, China
| | - Li-Qiang Qin
- Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Ren'ai Road, Suzhou 215123, China.
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11
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Guo Q, Dong Q, Xu W, Zhang H, Zhao X, He W, He Y, Zhao G. Metabolite profiling of camel milk and the fermentation bacteria agent TR1 fermented two types of sour camel milk using LC-MS in relation to their probiotic potentials. Heliyon 2024; 10:e35801. [PMID: 39220917 PMCID: PMC11365327 DOI: 10.1016/j.heliyon.2024.e35801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 07/13/2024] [Accepted: 08/05/2024] [Indexed: 09/04/2024] Open
Abstract
Camel milk is a nutrient-rich diet and fermentation affects its nutritional value and probiotic function. In this study, sour camel milk and oat jujube sour camel milk were prepared using fermentation bacteria agent TR1, and the metabolites of camel milk, sour camel milk and oat jujube sour camel milk were detected using a non-targeted metabolomics approach using liquid chromatography-mass spectrometry (LC-MS).The results showed that the partial least squares discriminant analysis (PLS-DA) with 100 % accuracy and good predictive power detected 343 components in positive ion mode and 220 components in negative ion mode. The differential metabolites were mainly organic acids, amino acids, esters, vitamins and other substances contained in camel milk.It showed that there were significant differences in the metabolites of camel milk, sour camel milk and oat jujube sour camel milk. Based on the pathway enrichment analysis of the three dairy products in the KEGG database, 12 metabolic pathways mainly involved in the positive ion mode and 20 metabolic pathways mainly involved in the negative ion mode were identified. The main biochemical metabolic pathways and signal transduction pathways of the differential metabolites of the three dairy products were obtained. This study provides theoretical support for improving the nutritional quality and probiotic function of camel milk and fermented camel milk products and provides a basis for the development of relevant processing technologies and products for camel milk and fermented camel milk.
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Affiliation(s)
- Qingwen Guo
- College of Life Sciences, Inner Mongolia Agricultural University, Hohhot 010018, China
- Key Laboratory of Biological Manufacturing in Inner Mongolia Autonomous Region, Inner Mongolia Agricultural University, Hohhot, China
| | - Qigeqi Dong
- College of Life Sciences, Inner Mongolia Agricultural University, Hohhot 010018, China
- Key Laboratory of Biological Manufacturing in Inner Mongolia Autonomous Region, Inner Mongolia Agricultural University, Hohhot, China
| | - Weisheng Xu
- College of Life Sciences, Inner Mongolia Agricultural University, Hohhot 010018, China
- Key Laboratory of Biological Manufacturing in Inner Mongolia Autonomous Region, Inner Mongolia Agricultural University, Hohhot, China
| | - Heping Zhang
- College of Food Science and Engineering, Inner Mongolia Agricultural University, Hohhot, China
| | - Xiangyu Zhao
- The People's Bank of China Operation Office, China
| | - Wanxiong He
- Inner Mongolia Medical University, Hohhot, China
| | - Yuxing He
- College of Food Science and Engineering, Inner Mongolia Agricultural University, Hohhot, China
| | - Guofen Zhao
- College of Life Sciences, Inner Mongolia Agricultural University, Hohhot 010018, China
- Key Laboratory of Biological Manufacturing in Inner Mongolia Autonomous Region, Inner Mongolia Agricultural University, Hohhot, China
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12
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Choi YJ, Kim Y, Hwang S. Role of Neutrophils in the Development of Steatotic Liver Disease. Semin Liver Dis 2024; 44:300-318. [PMID: 39117322 DOI: 10.1055/s-0044-1789207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/10/2024]
Abstract
This review explores the biological aspects of neutrophils, their contributions to the development of steatotic liver disease, and their potential as therapeutic targets for the disease. Although alcohol-associated and metabolic dysfunction-associated liver diseases originate from distinct etiological factors, the two diseases frequently share excessive lipid accumulation as a common contributor to their pathogenesis, thereby classifying them as types of steatotic liver disease. Dysregulated lipid deposition in the liver induces hepatic injury, triggering the activation of the innate immunity, partially through neutrophil recruitment. Traditionally recognized for their role in microbial clearance, neutrophils have recently garnered attention for their involvement in sterile inflammation, a pivotal component of steatotic liver disease pathogenesis. In conclusion, technological innovations, including single-cell RNA sequencing, have gradually disclosed the existence of various neutrophil subsets; however, how the distinct subsets of neutrophil population contribute differentially to the development of steatotic liver disease remains unclear.
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Affiliation(s)
- You-Jin Choi
- College of Pharmacy, Daegu Catholic University, Gyeongsan, Republic of Korea
| | - Yeonsoo Kim
- College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, Republic of Korea
| | - Seonghwan Hwang
- College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, Republic of Korea
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13
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Shawky LM, Abo El Wafa SM, Behery M, Bahr MH, Abu Alnasr MT, Morsi AA. Lactobacillus rhamnosus GG and Tannic Acid Synergistically Promote the Gut Barrier Integrity in a Rat Model of Experimental Diarrhea via Selective Immunomodulatory Cytokine Targeting. Mol Nutr Food Res 2024; 68:e2400295. [PMID: 39034291 DOI: 10.1002/mnfr.202400295] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Revised: 06/20/2024] [Indexed: 07/23/2024]
Abstract
SCOPE Diarrhea is a common health issue that contributes to a significant annual death rate among children and the elderly worldwide. The anti-diarrheal activity of Lactobacillus rhamnosus GG (LGG) and tannic acid (TA), alone or combined, is examined, in addition to their effect on intestinal barrier integrity. METHODS AND RESULTS Fifty-six adult male Wistar rats are randomly assigned into seven groups: control, LGG alone, TA alone, diarrhea model, diarrhea+LGG, diarrhea+TA, and diarrhea+LGG+TA-treated groups. Diarrhea is induced by high-lactose diet (HLD) consumption. LGG (1x109 CFU/rat) and TA (100 mg Kg-1 d-1) were given orally 4 days after HLD feeding and continued for 10 days. Ileum specimens are processed for biochemical analysis of the local intestinal cytokines, polymerase chain reaction (PCR), and histological study. Also, immunohistochemistry-based identification of Proliferating Cell Nuclear Antigen (PCNA) and zonula occludens 1 (ZO-1) is performed. Compared to the diarrhea model group, both treatments maintain the intestinal mucosal structure and proliferative activity and preserve ZO-1 expression, with the combination group showing the maximal effect. However, LGG-treated diarrheic rats show a remarkable decrease in the intestinal tissue concentrations of tumor necrosis factor-alpha (TNF-α) and nuclear factor Kappa beta (NF-κB); meanwhile, TA treatment leads to a selective decrease of interferon-gamma (INF-γ) and transforming growth factor-beta (TGF-β1). CONCLUSION Individual LGG and TA treatments significantly alleviate diarrhea, probably through a selective immunomodulatory cytokine-dependent mechanism, while the combination of both synergistically maintains the intestinal mucosa by keeping the intestinal epithelial barrier function and regenerative capability.
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Affiliation(s)
- Lamiaa M Shawky
- Department of Histology and Cell Biology, Faculty of Medicine, Benha University, Benha, 13511, Egypt
| | - Sahar M Abo El Wafa
- Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Benha University, Benha, 13511, Egypt
| | - Maged Behery
- Department of Anatomy and Embryology, Faculty of Medicine, Benha University, Benha, 13511, Egypt
| | - Mohamed H Bahr
- Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, 11591, Egypt
- Department of Basic Medical Sciences, Vision Colleges, Riyadh, 11451, Saudi Arabia
| | | | - Ahmed A Morsi
- Department of Histology and Cell Biology, Faculty of Medicine, Fayoum University, Fayoum, 63511, Egypt
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14
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Tian R, Wang X, Tang S, Zhao L, Hao Y, Li R, Zhou X. Gut microbiota mediates the protective effects of β-hydroxybutyrate against cisplatin-induced acute kidney injury. Biomed Pharmacother 2024; 175:116752. [PMID: 38761425 DOI: 10.1016/j.biopha.2024.116752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 05/03/2024] [Accepted: 05/10/2024] [Indexed: 05/20/2024] Open
Abstract
The gut microbiota has been reported to be perturbed by chemotherapeutic agents and to modulate side effects. However, the critical role of β-hydroxybutyrate (BHB) in the regulation of the gut microbiota and the pathogenesis of chemotherapeutic agents related nephrotoxicity remains unknown. We conducted a comparative analysis of the composition and function of gut microbiota in healthy, cisplatin-challenged, BHB-treated, and high-fat diet-treated mice using 16 S rDNA gene sequencing. To understand the crucial involvement of intestinal flora in BHB's regulation of cisplatin -induced nephrotoxicity, we administered antibiotics to deplete the gut microbiota and performed fecal microbiota transplantation (FMT) before cisplatin administration. 16 S rDNA gene sequencing analysis demonstrated that both endogenous and exogenous BHB restored gut microbiota dysbiosis and cisplatin-induced intestinal barrier disruption in mice. Additionally, our findings suggested that the LPS/TLR4/NF-κB pathway was responsible for triggering renal inflammation in the gut-kidney axis. Furthermore, the ablation of the gut microbiota ablation using antibiotics eliminated the renoprotective effects of BHB against cisplatin-induced acute kidney injury. FMT also confirmed that administration of BHB-treated gut microbiota provided protection against cisplatin-induced nephrotoxicity. This study elucidated the mechanism by which BHB affects the gut microbiota mediation of cisplatin-induced nephrotoxicity by inhibiting the inflammatory response, which may help develop novel therapeutic approaches that target the composition of the microbiota.
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Affiliation(s)
- Ruixue Tian
- The Fifth Clinical Medical College of Shanxi Medical University, 29 Shuang Ta East Street, Taiyuan 030012, China; Department of Nephrology, Shanxi Provincial People's Hospital, Taiyuan 030012, China
| | - Xingru Wang
- The Fifth Clinical Medical College of Shanxi Medical University, 29 Shuang Ta East Street, Taiyuan 030012, China; Department of Nephrology, Shanxi Provincial People's Hospital, Taiyuan 030012, China
| | - Shuqin Tang
- The Fifth Clinical Medical College of Shanxi Medical University, 29 Shuang Ta East Street, Taiyuan 030012, China; Department of Nephrology, Shanxi Provincial People's Hospital, Taiyuan 030012, China
| | - Limei Zhao
- The Fifth Clinical Medical College of Shanxi Medical University, 29 Shuang Ta East Street, Taiyuan 030012, China; Department of Nephrology, Shanxi Provincial People's Hospital, Taiyuan 030012, China
| | - Yajie Hao
- The Fifth Clinical Medical College of Shanxi Medical University, 29 Shuang Ta East Street, Taiyuan 030012, China; Department of Nephrology, Shanxi Provincial People's Hospital, Taiyuan 030012, China
| | - Rongshan Li
- The Fifth Clinical Medical College of Shanxi Medical University, 29 Shuang Ta East Street, Taiyuan 030012, China; Department of Nephrology, Shanxi Provincial People's Hospital, Taiyuan 030012, China; Shanxi Kidney Disease Institute, 29 Shuang Ta East Street, Taiyuan 030012, China
| | - Xiaoshuang Zhou
- The Fifth Clinical Medical College of Shanxi Medical University, 29 Shuang Ta East Street, Taiyuan 030012, China; Department of Nephrology, Shanxi Provincial People's Hospital, Taiyuan 030012, China; Shanxi Kidney Disease Institute, 29 Shuang Ta East Street, Taiyuan 030012, China.
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15
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Wei L, Pan Y, Guo Y, Zhu Y, Jin H, Gu Y, Li C, Wang Y, Lin J, Chen Y, Ke C, Xu L. Symbiotic combination of Akkermansia muciniphila and inosine alleviates alcohol-induced liver injury by modulating gut dysbiosis and immune responses. Front Microbiol 2024; 15:1355225. [PMID: 38572243 PMCID: PMC10987824 DOI: 10.3389/fmicb.2024.1355225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Accepted: 03/04/2024] [Indexed: 04/05/2024] Open
Abstract
Background Alcoholic liver disease (ALD) is exacerbated by disruptions in intestinal microecology and immune imbalances within the gut-liver axis. The present study assesses the therapeutic potential of combining Akkermansia muciniphila (A. muciniphila) with inosine in alleviating alcohol-induced liver injury. Methods Male C57BL/6 mice, subjected to a Lieber-DeCarli diet with 5% alcohol for 4 weeks, served as the alcoholic liver injury model. Various analyzes, including quantitative reverse transcription polymerase chain reaction (qRT-PCR), ELISA, immunochemistry, 16S rRNA gene sequencing, and flow cytometry, were employed to evaluate liver injury parameters, intestinal barrier function, microbiota composition, and immune responses. Results Compared to the model group, the A. muciniphila and inosine groups exhibited significantly decreased alanine aminotransferase, aspartate aminotransferase, and lipopolysaccharide (LPS) levels, reduced hepatic fat deposition and neutrophil infiltration, alleviated oxidative stress and inflammation, and increased expression of intestinal tight junction proteins (Claudin-1, Occludin, and ZO-1). These effects were further pronounced in the A. muciniphila and inosine combination group compared to individual treatments. While alcohol feeding induced intestinal dysbiosis and gut barrier disruption, the combined treatment reduced the abundance of harmful bacteria (Oscillibacter, Escherichia/Shigella, and Alistipes) induced by alcohol consumption, promoting the growth of butyrate-producing bacteria (Akkermansia, Lactobacillus, and Clostridium IV). Flow cytometry revealed that alcohol consumption reduced T regulatory (Treg) populations while increasing those of T-helper (Th) 1 and Th17, which were restored by A. muciniphila combined with inosine treatment. Moreover, A. muciniphila and inosine combination increased the expression levels of intestinal CD39, CD73, and adenosine A2A receptor (A2AR) along with enhanced proportions of CD4+CD39+Treg and CD4+CD73+Treg cells in the liver and spleen. The A2AR antagonist KW6002, blocked the beneficial effects of the A. muciniphila and inosine combination on liver injury in ALD mice. Conclusion This study reveals that the combination of A. muciniphila and inosine holds promise for ameliorating ALD by enhancing the gut ecosystem, improving intestinal barrier function, upregulating A2AR, CD73, and CD39 expression, modulating Treg cells functionality, and regulating the imbalance of Treg/Th17/Th1 cells, and these beneficial effects are partly A2AR-dependent.
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Affiliation(s)
- Li Wei
- Department of Infectious Diseases and Liver Diseases, Ningbo Medical Center Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
| | - Yizhi Pan
- Department of Infectious Diseases and Liver Diseases, Ningbo Medical Center Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
| | - Yu Guo
- Department of Infectious Diseases and Liver Diseases, Ningbo Medical Center Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
| | - Yin Zhu
- Hepatology Diagnosis and Treatment Center, The First Affiliated Hospital of Wenzhou Medical University & Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Wenzhou, China
- Department of Infectious Diseases, Taizhou Enze Medical Center (Group), Enze Hospital, Taizhou, China
| | - Haoran Jin
- Department of Infectious Diseases and Liver Diseases, Ningbo Medical Center Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
| | - Yingying Gu
- Department of Infectious Diseases and Liver Diseases, Ningbo Medical Center Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
| | - Chuanshuang Li
- Department of Infectious Diseases and Liver Diseases, Ningbo Medical Center Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
| | - Yaqin Wang
- Department of Infectious Diseases and Liver Diseases, Ningbo Medical Center Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
| | - Jingjing Lin
- Department of Infectious Diseases and Liver Diseases, Ningbo Medical Center Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
| | - Yongping Chen
- Hepatology Diagnosis and Treatment Center, The First Affiliated Hospital of Wenzhou Medical University & Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Wenzhou, China
| | - Chunhai Ke
- Department of Infectious Diseases and Liver Diseases, Ningbo Medical Center Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
- Hepatology Diagnosis and Treatment Center, The First Affiliated Hospital of Wenzhou Medical University & Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Wenzhou, China
| | - Lanman Xu
- Department of Infectious Diseases and Liver Diseases, Ningbo Medical Center Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
- Hepatology Diagnosis and Treatment Center, The First Affiliated Hospital of Wenzhou Medical University & Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Wenzhou, China
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16
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Sosnowski K, Przybyłkowski A. Ethanol-induced changes to the gut microbiome compromise the intestinal homeostasis: a review. Gut Microbes 2024; 16:2393272. [PMID: 39224006 PMCID: PMC11376419 DOI: 10.1080/19490976.2024.2393272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 08/06/2024] [Accepted: 08/12/2024] [Indexed: 09/04/2024] Open
Abstract
The intestine is the largest organ in terms of surface area in the human body. It is responsible not only for absorbing nutrients but also for protection against the external world. The gut microbiota is essential in maintaining a properly functioning intestinal barrier, primarily through producing its metabolites: short-chain fatty acids, bile acids, and tryptophan derivatives. Ethanol overconsumption poses a significant threat to intestinal health. Not only does it damage the intestinal epithelium, but, maybe foremostly, it changes the gut microbiome. Those ethanol-driven changes shift its metabolome, depriving the host of the protective effect the physiological gut microbiota has. This literature review discusses the impact of ethanol consumption on the gut, the gut microbiota, and its metabolome, providing a comprehensive overview of the mechanisms through which ethanol disrupts intestinal homeostasis and discussing potential avenues for new therapeutic intervention.
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Affiliation(s)
- Konrad Sosnowski
- Department of Gastroenterology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Adam Przybyłkowski
- Department of Gastroenterology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
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17
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Guo X, Liang K, Xia L, Zhang X, Liu J, Wang C, Li J, Li X, Hou X, Chen L. Mof plays distinct roles in hepatic lipid metabolism under healthy or non-alcoholic fatty liver conditions. iScience 2023; 26:108446. [PMID: 38034359 PMCID: PMC10687339 DOI: 10.1016/j.isci.2023.108446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 09/11/2023] [Accepted: 11/09/2023] [Indexed: 12/02/2023] Open
Abstract
The disturbance of hepatic lipid metabolism has a strong association with non-alcoholic fatty liver disease (NAFLD) and diabetes. Mof, an acetyltransferase involved in obesity and carbon metabolism, has not been thoroughly examined in its connection to hepatic metabolism. We aimed to explore the impact of Mof on hepatic lipid metabolism. The alteration of Mof expression was found in both obese mice and NAFLD human liver. The genes regulated by Mof were closely associated with lipid metabolism. In normal mice or hepatic cells, the down-regulation or inhibition of Mof resulted in increased lipid accumulation due to decreased PPARα expression. Conversely, in diet-induced obesity (DIO) mice or hepatic cells treated with palmitic acid, the inhibition of Mof led to improved lipid metabolism, attributed to the reduction in p-mTOR/mTOR levels. In summary, Mof exhibited distinct roles in lipid metabolism under different conditions. The inhibition of Mof may hold potential as a therapeutic target for hepatic lipid metabolism disturbances.
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Affiliation(s)
- Xinghong Guo
- Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
- Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, Shandong 250012, China
- Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, Shandong 250012, China
- Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, Shandong 250012, China
| | - Kai Liang
- Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
- Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, Shandong 250012, China
- Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, Shandong 250012, China
- Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, Shandong 250012, China
| | - Longqing Xia
- Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
| | - Xu Zhang
- Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Life Science School of Shandong University, Qingdao, Shandong 266237, China
| | - Jinbo Liu
- Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
- Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, Shandong 250012, China
- Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, Shandong 250012, China
- Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, Shandong 250012, China
| | - Chuan Wang
- Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
- Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, Shandong 250012, China
- Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, Shandong 250012, China
- Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, Shandong 250012, China
| | - Jinquan Li
- Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
- Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, Shandong 250012, China
- Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, Shandong 250012, China
- Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, Shandong 250012, China
| | - Xiangzhi Li
- Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Life Science School of Shandong University, Qingdao, Shandong 266237, China
| | - Xinguo Hou
- Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
- Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, Shandong 250012, China
- Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, Shandong 250012, China
- Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, Shandong 250012, China
| | - Li Chen
- Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
- Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, Shandong 250012, China
- Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, Shandong 250012, China
- Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, Shandong 250012, China
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18
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Zhou QM, Zheng L. Research progress on the relationship between Paneth cells-susceptibility genes, intestinal microecology and inflammatory bowel disease. World J Clin Cases 2023; 11:8111-8125. [PMID: 38130785 PMCID: PMC10731169 DOI: 10.12998/wjcc.v11.i34.8111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 09/26/2023] [Accepted: 11/27/2023] [Indexed: 12/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a disorder of the immune system and intestinal microecosystem caused by environmental factors in genetically susceptible people. Paneth cells (PCs) play a central role in IBD pathogenesis, especially in Crohn's disease development, and their morphology, number and function are regulated by susceptibility genes. In the intestine, PCs participate in the formation of the stem cell microenvironment by secreting antibacterial particles and play a role in helping maintain the intestinal microecology and intestinal mucosal homeostasis. Moreover, PC proliferation and maturation depend on symbiotic flora in the intestine. This paper describes the interactions among susceptibility genes, PCs and intestinal microecology and their effects on IBD occurrence and development.
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Affiliation(s)
- Qi-Ming Zhou
- Department of Nephrology, Lanxi Hospital of Traditional Chinese Medicine, Lanxi 321100, Zhejiang Province, China
| | - Lie Zheng
- Department of Gastroenterology, Shaanxi Hospital of Traditional Chinese Medicine, Xi’an 710003, Shaanxi Province, China
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19
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Yazici D, Ogulur I, Pat Y, Babayev H, Barletta E, Ardicli S, Bel Imam M, Huang M, Koch J, Li M, Maurer D, Radzikowska U, Satitsuksanoa P, Schneider SR, Sun N, Traidl S, Wallimann A, Wawrocki S, Zhakparov D, Fehr D, Ziadlou R, Mitamura Y, Brüggen MC, van de Veen W, Sokolowska M, Baerenfaller K, Nadeau K, Akdis M, Akdis CA. The epithelial barrier: The gateway to allergic, autoimmune, and metabolic diseases and chronic neuropsychiatric conditions. Semin Immunol 2023; 70:101846. [PMID: 37801907 DOI: 10.1016/j.smim.2023.101846] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 09/27/2023] [Indexed: 10/08/2023]
Abstract
Since the 1960 s, our health has been compromised by exposure to over 350,000 newly introduced toxic substances, contributing to the current pandemic in allergic, autoimmune and metabolic diseases. The "Epithelial Barrier Theory" postulates that these diseases are exacerbated by persistent periepithelial inflammation (epithelitis) triggered by exposure to a wide range of epithelial barrier-damaging substances as well as genetic susceptibility. The epithelial barrier serves as the body's primary physical, chemical, and immunological barrier against external stimuli. A leaky epithelial barrier facilitates the translocation of the microbiome from the surface of the afflicted tissues to interepithelial and even deeper subepithelial locations. In turn, opportunistic bacterial colonization, microbiota dysbiosis, local inflammation and impaired tissue regeneration and remodelling follow. Migration of inflammatory cells to susceptible tissues contributes to damage and inflammation, initiating and aggravating many chronic inflammatory diseases. The objective of this review is to highlight and evaluate recent studies on epithelial physiology and its role in the pathogenesis of chronic diseases in light of the epithelial barrier theory.
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Affiliation(s)
- Duygu Yazici
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Ismail Ogulur
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Yagiz Pat
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Huseyn Babayev
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Elena Barletta
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; Swiss Institute of Bioinformatics (SIB), Davos, Switzerland
| | - Sena Ardicli
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Manal Bel Imam
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Mengting Huang
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Jana Koch
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; Swiss Institute of Bioinformatics (SIB), Davos, Switzerland
| | - Manru Li
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Debbie Maurer
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Urszula Radzikowska
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland
| | | | - Stephan R Schneider
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Na Sun
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, PR China
| | - Stephan Traidl
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany
| | - Alexandra Wallimann
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Sebastian Wawrocki
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Damir Zhakparov
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Danielle Fehr
- Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland; Faculty of Medicine, University of Zurich, Zurich, Switzerland; Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
| | - Reihane Ziadlou
- Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland; Faculty of Medicine, University of Zurich, Zurich, Switzerland; Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
| | - Yasutaka Mitamura
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Marie-Charlotte Brüggen
- Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland; Faculty of Medicine, University of Zurich, Zurich, Switzerland; Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
| | - Willem van de Veen
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland
| | - Milena Sokolowska
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland
| | - Katja Baerenfaller
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; Swiss Institute of Bioinformatics (SIB), Davos, Switzerland
| | - Kari Nadeau
- Department of Environmental Health, T.H. Chan School of Public Health, Harvard University, Boston, MA, USA
| | - Mubeccel Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Cezmi A Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland.
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20
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Wen X, Wang Z, Liu Q, Lessing DJ, Chu W. Acetobacter pasteurianus BP2201 alleviates alcohol-induced hepatic and neuro-toxicity and modulate gut microbiota in mice. Microb Biotechnol 2023; 16:1834-1857. [PMID: 37354051 PMCID: PMC10443346 DOI: 10.1111/1751-7915.14303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 06/10/2023] [Accepted: 06/13/2023] [Indexed: 06/26/2023] Open
Abstract
The excessive consumption of alcohol results in a dysbiosis of the gut microbiota, which subsequently impairs the gut microbiota-brain/liver axes and induces cognitive dysfunction and hepatic injury. This study aimed to investigate the potential effect of Acetobacter pasteurianus BP2201 in reducing the negative effects of alcohol consumption on cognitive function and liver health by modulating the gut microbiota-brain/liver axes. Treatment with A. pasteurianus BP2201 improved alcohol-induced hippocampal damage, suppressed neuroinflammation, promoted neuroprotein expression in the hippocampus and enhanced cognitive function. At the same time, A. pasteurianus BP2201 can also reduce serum lipid levels, relieve oxidative stress, inhibit TLR4/MyD88/NF-κB pathway, reduce the secretion of TNF-α and IL-1β, so as to improve alcoholic liver injury. Concomitantly, the treatment with A. pasteurianus BP2201 leads to a shift in the intestinal microbiota structure towards that of healthy individuals, inhibiting the proliferation of harmful bacteria and promoting the recovery of beneficial bacteria. In addition, it also improves brain cognitive dysfunction and liver health by affecting the gut microbiota-brain/liver axes by promoting the synthesis of relevant amino acids and the metabolism of nucleotide base components. These findings demonstrate the potential of regulating the gut microbiome and gut microbiota-brain/liver axes to mitigate alcohol-induced disease.
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Affiliation(s)
- Xin Wen
- Department of Pharmaceutical Microbiology, School of Life Science and TechnologyChina Pharmaceutical UniversityNanjingChina
| | - Zheng Wang
- Department of Pharmaceutical Microbiology, School of Life Science and TechnologyChina Pharmaceutical UniversityNanjingChina
| | - Qi Liu
- Department of Pharmaceutical Microbiology, School of Life Science and TechnologyChina Pharmaceutical UniversityNanjingChina
| | - Duncan James Lessing
- Department of Pharmaceutical Microbiology, School of Life Science and TechnologyChina Pharmaceutical UniversityNanjingChina
| | - Weihua Chu
- Department of Pharmaceutical Microbiology, School of Life Science and TechnologyChina Pharmaceutical UniversityNanjingChina
- State Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjingChina
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21
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Wang H, Fu Y, Zhao Q, Liu Z, Wang C, Xue Y, Shen Q. Effects of heat-treated starch and protein from foxtail millet (Setaria italica) on type 2 diabetic mice. Food Chem 2023; 404:134735. [DOI: 10.1016/j.foodchem.2022.134735] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 10/17/2022] [Accepted: 10/22/2022] [Indexed: 11/04/2022]
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Chen L, Yang P, Hu L, Yang L, Chu H, Hou X. Modulating phenylalanine metabolism by L. acidophilus alleviates alcohol-related liver disease through enhancing intestinal barrier function. Cell Biosci 2023; 13:24. [PMID: 36739426 PMCID: PMC9899391 DOI: 10.1186/s13578-023-00974-z] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Accepted: 01/27/2023] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Impaired metabolic functions of gut microbiota have been demonstrated in alcohol-related liver disease (ALD), but little is known about changes in phenylalanine metabolism. METHODS Bacterial genomics and fecal metabolomics analysis were used to recognize the changes of phenylalanine metabolism and its relationship with intestinal flora. Intestinal barrier function was detected by intestinal alkaline phosphatase (IAP) activity, levels of tight junction protein expression, colonic inflammation and levels of serum LPS. Lactobacillus acidophilus was chosen to correct phenylalanine metabolism of ALD mice by redundancy analysis and Pearson correlation analysis. RESULTS Using 16S rRNA sequencing and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methods, we identified elevated levels of phenylalanine and its' metabolites in the gut of alcohol-fed mice compared to control mice and were negatively correlated with the abundance of Lactobacillus, which mainly metabolized phenylalanine. The intestinal phenylalanine level was positively correlated with the colon inflammatory factors TNF-α and IL-6, and negatively correlated with ZO-1 and Occludin. While intestinal alkaline phosphatase (IAP) activity was negatively correlated with the colon inflammatory factors TNF-α, IL-6 and MCP-1, and positively correlated with ZO-1 and Occludin. Increased phenylalanine inhibited IAP activity, blocked LPS dephosphorylation, increased colonic inflammation and bacterial translocation. Phenylalanine supplementation aggravated alcohol-induced liver injury and intestinal barrier dysfunction. Among the 37 Lactobacillus species, the abundance of Lactobacillus acidophilus was most significantly decreased in ALD mice. Supplementation with L. acidophilus recovered phenylalanine metabolism and protected mice from alcohol-induced steatohepatitis. CONCLUSIONS Recovery of phenylalanine metabolism through the oral supplementation of L. acidophilus boosted intestinal barrier integrity and ameliorated experimental ALD.
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Affiliation(s)
- Liuying Chen
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China
| | - Pengcheng Yang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China
| | - Lilin Hu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China
| | - Ling Yang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China
| | - Huikuan Chu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.
| | - Xiaohua Hou
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.
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23
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Liu Y, Zhang D, Ning Q, Wang J. Growth characteristics and metabonomics analysis of Lactobacillus rhamnosus GG in Ganoderma lucidum aqueous extract medium. FOOD BIOSCI 2023. [DOI: 10.1016/j.fbio.2023.102486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/26/2023]
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24
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Liu Y, Xue Y, Zhang Z, Ji J, Li C, Zheng K, Lu J, Gao Y, Gong Y, Zhang Y, Shi X. Wolfberry enhanced the abundance of Akkermansia muciniphila by YAP1 in mice with acetaminophen-induced liver injury. FASEB J 2023; 37:e22689. [PMID: 36468767 DOI: 10.1096/fj.202200945r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 10/18/2022] [Accepted: 11/21/2022] [Indexed: 12/12/2022]
Abstract
Drug-induced liver injury (DILI) by acetaminophen (APAP) was one of the most challenging liver diseases. Wolfberry (Lycium barbarum L.), a traditional Chinese medicinal material and food supplement, has a potential effect on increasing the abundance of Akkermansia muciniphila (A. muciniphila) in mice colons. However, the effect and mechanism of wolfberry remain unclear in APAP-induced DILI. In this study, wolfberry promoted the proliferation of activated-A. muciniphila in vitro and in vivo. For the first time, we detected that the activated-A. muciniphila but not the killed-A. muciniphila increased the expression level of Yes-associated protein 1 (YAP1) in the liver and alleviated liver injury in APAP-induced DILI mice. Mechanically, A. muciniphila improved the intestinal mucosal barrier and reduced lipopolysaccharide (LPS) content in the liver, leading to the increased expression level of YAP1. Furthermore, wolfberry increased the A. muciniphila abundance in the colon and YAP1 expression in the liver from APAP-induced DILI mice, which promoted the recovery of APAP-induced liver injury. Meanwhile, wolfberry combination with A. muciniphila synergistically increased AKK abundance and YAP1 expression in the liver. Our research provides an innovative strategy to improve DILI.
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Affiliation(s)
- Yiwei Liu
- Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Yu Xue
- Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Zhiqin Zhang
- Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Jingmin Ji
- Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Caige Li
- Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Kangning Zheng
- Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Junlan Lu
- Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Yuting Gao
- Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Yi Gong
- Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Yuman Zhang
- Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Xinli Shi
- Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, China
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25
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Zaccaria E, Klaassen T, Alleleyn AM, Boekhorst J, Chervaux C, Smokvina T, Troost FJ, Kleerebezem M. L. rhamnosus CNCM I-3690 survival, adaptation, and small bowel microbiome impact in human. Gut Microbes 2023; 15:2244720. [PMID: 37589280 PMCID: PMC10438856 DOI: 10.1080/19490976.2023.2244720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 07/05/2023] [Accepted: 08/01/2023] [Indexed: 08/18/2023] Open
Abstract
Fermented foods and beverages are a significant source of dietary bacteria that enter the gastrointestinal (GI) tract. However, little is known about how these microbes survive and adapt to the small intestinal environment. Colony-forming units (CFU) enumeration and viability qPCR of Lacticaseibacillus rhamnosus CNCM I-3690 in the ileal effluent of 10 ileostomy subjects during 12-h post consumption of a dairy product fermented with this strain demonstrated the high level of survival of this strain during human small intestine passage. Metatranscriptome analyses revealed the in situ transcriptome of L. rhamnosus in the small intestine, which was contrasted with transcriptome data obtained from in vitro cultivation. These comparative analyses revealed substantial metabolic adaptations of L. rhamnosus during small intestine transit, including adjustments of carbohydrate metabolism, surface-protein expression, and translation machinery. The prominent presence of L. rhamnosus in the effluent samples did not elicit an appreciable effect on the composition of the endogenous small intestine microbiome, but significantly altered the ecosystem's overall activity profile, particularly of pathways associated with carbohydrate metabolism. Strikingly, two of the previously recognized gut-brain metabolic modules expressed in situ by L. rhamnosus (inositol degradation and glutamate synthesis II) are among the most dominantly enriched activities in the ecosystem's activity profile. This study establishes the survival capacity of L. rhamnosus in the human small intestine and highlights its functional adjustment in situ, which we postulate to play a role in the probiotic effects associated with this strain.
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Affiliation(s)
- Edoardo Zaccaria
- Host Microbe Interactomics Group, Wageningen University & Research, Wageningen, The Netherlands
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Tim Klaassen
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, Maastricht, The Netherlands
- Food Innovation and Health, Department of Human Biology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Venlo, The Netherlands
| | - Annick M.E. Alleleyn
- Food Innovation and Health, Department of Human Biology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Venlo, The Netherlands
| | - Jos Boekhorst
- Host Microbe Interactomics Group, Wageningen University & Research, Wageningen, The Netherlands
| | | | - Tamara Smokvina
- Danone Nutricia Research, Centre Daniel Carasso, Palaiseau, France
| | - Freddy J. Troost
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Michiel Kleerebezem
- Host Microbe Interactomics Group, Wageningen University & Research, Wageningen, The Netherlands
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26
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Zhou Z, Pan X, Li L. Crosstalk between liver macrophages and gut microbiota: An important component of inflammation-associated liver diseases. Front Cell Dev Biol 2022; 10:1070208. [PMID: 36483677 PMCID: PMC9723159 DOI: 10.3389/fcell.2022.1070208] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Accepted: 11/10/2022] [Indexed: 08/30/2023] Open
Abstract
Hepatic macrophages have been recognized as primary sensors and responders in liver inflammation. By processing host or exogenous biochemical signals, including microbial components and metabolites, through the gut-liver axis, hepatic macrophages can both trigger or regulate inflammatory responses. Crosstalk between hepatic macrophages and gut microbiota is an important component of liver inflammation and related liver diseases, such as acute liver injury (ALI), alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD). This review summarizes recent advances in knowledge related to the crosstalk between hepatic macrophages and gut microbiota, including the therapeutic potential of targeting hepatic macrophages as a component of gut microecology in inflammation-associated liver diseases.
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Affiliation(s)
| | | | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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27
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Kim IS, Jo EK. Inosine: A bioactive metabolite with multimodal actions in human diseases. Front Pharmacol 2022; 13:1043970. [PMID: 36467085 PMCID: PMC9708727 DOI: 10.3389/fphar.2022.1043970] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Accepted: 11/02/2022] [Indexed: 08/04/2023] Open
Abstract
The nucleoside inosine is an essential metabolite for purine biosynthesis and degradation; it also acts as a bioactive molecule that regulates RNA editing, metabolic enzyme activity, and signaling pathways. As a result, inosine is emerging as a highly versatile bioactive compound and second messenger of signal transduction in cells with diverse functional abilities in different pathological states. Gut microbiota remodeling is closely associated with human disease pathogenesis and responses to dietary and medical supplementation. Recent studies have revealed a critical link between inosine and gut microbiota impacting anti-tumor, anti-inflammatory, and antimicrobial responses in a context-dependent manner. In this review, we summarize the latest progress in our understanding of the mechanistic function of inosine, to unravel its immunomodulatory actions in pathological settings such as cancer, infection, inflammation, and cardiovascular and neurological diseases. We also highlight the role of gut microbiota in connection with inosine metabolism in different pathophysiological conditions. A more thorough understanding of the mechanistic roles of inosine and how it regulates disease pathologies will pave the way for future development of therapeutic and preventive modalities for various human diseases.
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Affiliation(s)
- In Soo Kim
- Department of Medical Science, Chungnam National University College of Medicine, Daejeon, South Korea
- Department of Microbiology, Chungnam National University College of Medicine, Daejeon, South Korea
- Infection Control Convergence Research Center, Chungnam National University College of Medicine, Daejeon, South Korea
| | - Eun-Kyoung Jo
- Department of Medical Science, Chungnam National University College of Medicine, Daejeon, South Korea
- Department of Microbiology, Chungnam National University College of Medicine, Daejeon, South Korea
- Infection Control Convergence Research Center, Chungnam National University College of Medicine, Daejeon, South Korea
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Yang F, Zhou L, Shen Y, Zhao S, Zheng Y, Men R, Fan X, Yang L. Metabolic heterogeneity caused by HLA-DRB1*04:05 and protective effect of inosine on autoimmune hepatitis. Front Immunol 2022; 13:982186. [PMID: 35990653 PMCID: PMC9389112 DOI: 10.3389/fimmu.2022.982186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 07/15/2022] [Indexed: 11/16/2022] Open
Abstract
Autoimmune hepatitis (AIH) is an autoimmune disease caused by disruption of liver immune homeostasis. Genetic studies have revealed the predisposition of AIH with the human leukocyte antigen (HLA) region. Recently, metabolomics integrated with genomics has identified many genetic loci of biomedical interest. However, there is no related report in AIH. In the present study, we found that HLA-DRB1*04:05 was linked to the clinical features and prognosis of AIH in Chinese patients. Furthermore, our patients were divided into DRB1*04:05 positive and DRB1*04:05 negative groups and the metabolic profiling was done by HPLC/MS. We chose inosine, one of the highly altered metabolites, to explore the effect on an acute severe hepatitis murine model. The results showed that inosine treatment attenuated hepatocyte apoptosis, enhanced antioxidant ability and inhibited the activation and glycolysis of CD4+ T cell. We propose that inosine participates in the regulation of AIH through its protective effect on hepatocytes and inhibition of overactivated immune cells, which might provide a potential novel approach in treating acute form of AIH.
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Affiliation(s)
| | | | | | | | | | | | | | - Li Yang
- *Correspondence: Li Yang, ; Xiaoli Fan,
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Chen G, Shi F, Yin W, Guo Y, Liu A, Shuai J, Sun J. Gut microbiota dysbiosis: The potential mechanisms by which alcohol disrupts gut and brain functions. Front Microbiol 2022; 13:916765. [PMID: 35966709 PMCID: PMC9372561 DOI: 10.3389/fmicb.2022.916765] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 06/29/2022] [Indexed: 11/24/2022] Open
Abstract
Alcohol use disorder (AUD) is a high-risk psychiatric disorder and a key cause of death and disability in individuals. In the development of AUD, there is a connection known as the microbiota-gut-brain axis, where alcohol use disrupts the gut barrier, resulting in changes in intestinal permeability as well as the gut microbiota composition, which in turn impairs brain function and worsens the patient’s mental status and gut activity. Potential mechanisms are explored by which alcohol alters gut and brain function through the effects of the gut microbiota and their metabolites on immune and inflammatory pathways. Alcohol and microbiota dysregulation regulating neurotransmitter release, including DA, 5-HT, and GABA, are also discussed. Thus, based on the above discussion, it is possible to speculate on the gut microbiota as an underlying target for the treatment of diseases associated with alcohol addiction. This review will focus more on how alcohol and gut microbiota affect the structure and function of the gut and brain, specific changes in the composition of the gut microbiota, and some measures to mitigate the changes caused by alcohol exposure. This leads to a potential intervention for alcohol addiction through fecal microbiota transplantation, which could normalize the disruption of gut microbiota after AUD.
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Affiliation(s)
- Ganggang Chen
- Department of Anatomy and Neurobiology, School of Basic Medicine, Shandong University, Jinan, China
| | - Fenglei Shi
- Department of Othopaedics, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Wei Yin
- Department of Anatomy and Neurobiology, School of Basic Medicine, Shandong University, Jinan, China
| | - Yao Guo
- Shandong Provincial Mental Health Center, Jinan, China
| | - Anru Liu
- Department of Anatomy and Neurobiology, School of Basic Medicine, Shandong University, Jinan, China
| | - Jiacheng Shuai
- Department of Anatomy and Neurobiology, School of Basic Medicine, Shandong University, Jinan, China
| | - Jinhao Sun
- Department of Anatomy and Neurobiology, School of Basic Medicine, Shandong University, Jinan, China
- *Correspondence: Jinhao Sun,
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Zafari N, Velayati M, Fahim M, Maftouh M, Pourali G, Khazaei M, Nassiri M, Hassanian SM, Ghayour-Mobarhan M, Ferns GA, Kiani MA, Avan A. Role of gut bacterial and non-bacterial microbiota in alcohol-associated liver disease: Molecular mechanisms, biomarkers, and therapeutic prospective. Life Sci 2022; 305:120760. [PMID: 35787997 DOI: 10.1016/j.lfs.2022.120760] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 06/20/2022] [Accepted: 06/28/2022] [Indexed: 12/17/2022]
Abstract
Alcohol-associated liver disease (ALD) comprises a spectrum of liver diseases that include: steatosis to alcohol-associated hepatitis, cirrhosis, and ultimately hepatocellular carcinoma. The pathophysiology and potential underlying mechanisms for alcohol-associated liver disease are unclear. Moreover, the treatment of ALD remains a challenge. Intestinal microbiota include bacteria, fungi, and viruses, that are now known to be important in the development of ALD. Alcohol consumption can change the gut microbiota and function leading to liver disease. Given the importance of interactions between intestinal microbiota, alcohol, and liver injury, the gut microbiota has emerged as a potential biomarker and therapeutic target. This review focuses on the potential mechanisms by which the gut microbiota may be involved in the pathogenesis of ALD and explains how this can be translated into clinical management. We discuss the potential of utilizing the gut microbiota signature as a biomarker in ALD patients. Additionally, we present an overview of the prospect of modulating the intestinal microbiota for the management of ALD.
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Affiliation(s)
- Nima Zafari
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahla Velayati
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mostafa Fahim
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mina Maftouh
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ghazaleh Pourali
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Khazaei
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammadreza Nassiri
- Recombinant Proteins Research Group, The Research Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Seyed Mahdi Hassanian
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Ghayour-Mobarhan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- Brighton & Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex BN1 9PH, UK
| | - Mohammad Ali Kiani
- Department of Pediatrics, Akbar Hospital, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pediatric Gastroenterology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Avan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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31
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Wang Z, Li F, Liu J, Luo Y, Guo H, Yang Q, Xu C, Ma S, Chen H. Intestinal Microbiota - An Unmissable Bridge to Severe Acute Pancreatitis-Associated Acute Lung Injury. Front Immunol 2022; 13:913178. [PMID: 35774796 PMCID: PMC9237221 DOI: 10.3389/fimmu.2022.913178] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 05/11/2022] [Indexed: 11/28/2022] Open
Abstract
Severe acute pancreatitis (SAP), one of the most serious abdominal emergencies in general surgery, is characterized by acute and rapid onset as well as high mortality, which often leads to multiple organ failure (MOF). Acute lung injury (ALI), the earliest accompanied organ dysfunction, is the most common cause of death in patients following the SAP onset. The exact pathogenesis of ALI during SAP, however, remains unclear. In recent years, advances in the microbiota-gut-lung axis have led to a better understanding of SAP-associated lung injury (PALI). In addition, the bidirectional communications between intestinal microbes and the lung are becoming more apparent. This paper aims to review the mechanisms of an imbalanced intestinal microbiota contributing to the development of PALI, which is mediated by the disruption of physical, chemical, and immune barriers in the intestine, promotes bacterial translocation, and results in the activation of abnormal immune responses in severe pancreatitis. The pathogen-associated molecular patterns (PAMPs) mediated immunol mechanisms in the occurrence of PALI via binding with pattern recognition receptors (PRRs) through the microbiota-gut-lung axis are focused in this study. Moreover, the potential therapeutic strategies for alleviating PALI by regulating the composition or the function of the intestinal microbiota are discussed in this review. The aim of this study is to provide new ideas and therapeutic tools for PALI patients.
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Affiliation(s)
- Zhengjian Wang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Fan Li
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Jin Liu
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yalan Luo
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Haoya Guo
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Qi Yang
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Caiming Xu
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, United States
| | - Shurong Ma
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- *Correspondence: Shurong Ma, ; Hailong Chen,
| | - Hailong Chen
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
- *Correspondence: Shurong Ma, ; Hailong Chen,
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